Upregulation of neuropeptide Y in cardiac sympathetic nerves induces stress (Takotsubo) cardiomyopathy
Substantial emotional or physical stress may lead to an imbalance in the brain, resulting in stress cardiomyopathy (SC) and transient left ventricular (LV) apical ballooning. Even though these conditions are severe, their precise underlying mechanisms remain unclear. Appropriate animal models are ne...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2022.1013712/full |
| _version_ | 1811331656118697984 |
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| author | Takahide Arai Takahide Arai Hideaki Kanazawa Kensuke Kimura Masahito Munakata Hiroyuki Yamakawa Ken Shinmura Shinsuke Yuasa Motoaki Sano Keiichi Fukuda |
| author_facet | Takahide Arai Takahide Arai Hideaki Kanazawa Kensuke Kimura Masahito Munakata Hiroyuki Yamakawa Ken Shinmura Shinsuke Yuasa Motoaki Sano Keiichi Fukuda |
| author_sort | Takahide Arai |
| collection | DOAJ |
| description | Substantial emotional or physical stress may lead to an imbalance in the brain, resulting in stress cardiomyopathy (SC) and transient left ventricular (LV) apical ballooning. Even though these conditions are severe, their precise underlying mechanisms remain unclear. Appropriate animal models are needed to elucidate the precise mechanisms. In this study, we established a new animal model of epilepsy-induced SC. The SC model showed an increased expression of the acute phase reaction protein, c-Fos, in the paraventricular hypothalamic nucleus (PVN), which is the sympathetic nerve center of the brain. Furthermore, we observed a significant upregulation of neuropeptide Y (NPY) expression in the left stellate ganglion (SG) and cardiac sympathetic nerves. NPY showed neither positive nor negative inotropic and chronotropic effects. On the contrary, NPY could interrupt β-adrenergic signaling in cardiomyocytes when exposure to NPY precedes exposure to noradrenaline. Moreover, its elimination in the left SG via siRNA treatment tended to reduce the incidence of SC. Thus, our results indicated that upstream sympathetic activation induced significant upregulation of NPY in the left SG and cardiac sympathetic nerves, resulting in cardiac dysfunctions like SC. |
| first_indexed | 2024-04-13T16:23:58Z |
| format | Article |
| id | doaj.art-6ff35c2021cc46ad88681f24821dda1c |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-13T16:23:58Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-6ff35c2021cc46ad88681f24821dda1c2022-12-22T02:39:48ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-11-011610.3389/fnins.2022.10137121013712Upregulation of neuropeptide Y in cardiac sympathetic nerves induces stress (Takotsubo) cardiomyopathyTakahide Arai0Takahide Arai1Hideaki Kanazawa2Kensuke Kimura3Masahito Munakata4Hiroyuki Yamakawa5Ken Shinmura6Shinsuke Yuasa7Motoaki Sano8Keiichi Fukuda9Division of Cardiology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, JapanInternational Medical Center, Department of Cardiology, Saitama Medical University, Saitama, JapanDivision of Cardiology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, JapanDepartment of Internal Medicine, Kimura Clinic, Kanagawa, JapanDivision of Cardiology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, JapanDivision of Cardiology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, JapanDepartment of General Internal Medicine, Hyogo College School of Medicine, Nishinomiya, JapanDivision of Cardiology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, JapanDivision of Cardiology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, JapanDivision of Cardiology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, JapanSubstantial emotional or physical stress may lead to an imbalance in the brain, resulting in stress cardiomyopathy (SC) and transient left ventricular (LV) apical ballooning. Even though these conditions are severe, their precise underlying mechanisms remain unclear. Appropriate animal models are needed to elucidate the precise mechanisms. In this study, we established a new animal model of epilepsy-induced SC. The SC model showed an increased expression of the acute phase reaction protein, c-Fos, in the paraventricular hypothalamic nucleus (PVN), which is the sympathetic nerve center of the brain. Furthermore, we observed a significant upregulation of neuropeptide Y (NPY) expression in the left stellate ganglion (SG) and cardiac sympathetic nerves. NPY showed neither positive nor negative inotropic and chronotropic effects. On the contrary, NPY could interrupt β-adrenergic signaling in cardiomyocytes when exposure to NPY precedes exposure to noradrenaline. Moreover, its elimination in the left SG via siRNA treatment tended to reduce the incidence of SC. Thus, our results indicated that upstream sympathetic activation induced significant upregulation of NPY in the left SG and cardiac sympathetic nerves, resulting in cardiac dysfunctions like SC.https://www.frontiersin.org/articles/10.3389/fnins.2022.1013712/fullneuropeptide Ycardiac sympathetic nervousstellate ganglionstressTakotsubo cardiomyopathy |
| spellingShingle | Takahide Arai Takahide Arai Hideaki Kanazawa Kensuke Kimura Masahito Munakata Hiroyuki Yamakawa Ken Shinmura Shinsuke Yuasa Motoaki Sano Keiichi Fukuda Upregulation of neuropeptide Y in cardiac sympathetic nerves induces stress (Takotsubo) cardiomyopathy Frontiers in Neuroscience neuropeptide Y cardiac sympathetic nervous stellate ganglion stress Takotsubo cardiomyopathy |
| title | Upregulation of neuropeptide Y in cardiac sympathetic nerves induces stress (Takotsubo) cardiomyopathy |
| title_full | Upregulation of neuropeptide Y in cardiac sympathetic nerves induces stress (Takotsubo) cardiomyopathy |
| title_fullStr | Upregulation of neuropeptide Y in cardiac sympathetic nerves induces stress (Takotsubo) cardiomyopathy |
| title_full_unstemmed | Upregulation of neuropeptide Y in cardiac sympathetic nerves induces stress (Takotsubo) cardiomyopathy |
| title_short | Upregulation of neuropeptide Y in cardiac sympathetic nerves induces stress (Takotsubo) cardiomyopathy |
| title_sort | upregulation of neuropeptide y in cardiac sympathetic nerves induces stress takotsubo cardiomyopathy |
| topic | neuropeptide Y cardiac sympathetic nervous stellate ganglion stress Takotsubo cardiomyopathy |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2022.1013712/full |
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